Caloosahatchee River watershed and estuary has experienced a general decline in the water quality over the last several decades due to agriculture practices, development, and other human activities. The objective of this study is to assess the water quality condition in coastal Caloosahatchee River watershed by analyzing the data collected by South Florida Water Management District and Lee County. Results indicated that during 1995 to 2006, averaged annually, Lake Okeechobee released 1124 million m3 of freshwater into the Caloosahatchee River, whereas the average annual freshwater discharge out of the Caloosahatchee River was approximately 2277 million m3. Lake Okeechobee might have more impacts on the water quality condition of Caloosahatchee River in dry season than wet season. The loads ratios of Lake Okeechobee to those out of Caloosahatchee River were much higher in dry season than wet season for flow (72% to 36%), total phosphorus (63% to 20%), total nitrogen (72% to 41%), organic nitrogen (85% to 47%), and NH3 (78% to 39%). In the coastal watershed area where the urban area is concentrated, of the total 5453 water samples, 74% of them have dissolved oxygen concentration less than 5 mg L(-1), the United States Environmental Protection Agency and Florida Department of Environmental Protection water quality standard. Only in January is the average monthly dissolved oxygen concentration higher than 5 mg L(-1).